Although CD8+ T cells are important in clearing viral infections, many subjects with CD8+ T cell immunodeficiencies have relatively mild disease. CD4+ cytolytic T cells have long been ignored and mistakenly viewed to be senescent cells. Recent studies in mice and humans have re- awakened interest in these cells and they are now recognized to have a distinct molecular developmental program and to be of relevance from a disease standpoint. Some data suggests that they cells may be potent at controlling HIV. Our goal in this application is understand the molecular basis for CD4+CTL induction especially in the context of HIV infection and its control. The long-term strategy is to rationally adjuvant HIV immunization soon after disease acquisition in order to effectively generate HIV-specific CD4+ CTLs that have the potential to clear the virus and/or prevent disease progression.